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有氧运动联合抗氧化治疗不能改善 APP/PS1 小鼠的中晚期阿尔茨海默病样病理生理学改变。

Aerobic exercise combined with antioxidative treatment does not counteract moderate- or mid-stage Alzheimer-like pathophysiology of APP/PS1 mice.

机构信息

Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

CNS Neurosci Ther. 2013 Oct;19(10):795-803. doi: 10.1111/cns.12139. Epub 2013 Jul 4.

Abstract

AIMS

The present study evaluated the combined treatment effects of aerobic exercise and antioxidative stress on moderate-stage Alzheimer's disease (AD).

METHODS

Ten-month-old APP/PS1 mice were given antioxidative treatment with acetylcysteine, along with aerobic exercise for 6 weeks. Spatial learning and memory were tested using the Morris water maze, and β-amyloid (Aβ) plaque deposits in the forebrain were quantified by Thioflavin-S staining. Levels of soluble Aβ1-42, β-secretase enzyme, ү-secretase enzyme, oxidative and antioxidant stress markers nitrotyrosine and peroxiredoxin-1, glial markers glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1, and synaptic protein synaptophysin in the hippocampus were all measured by western blotting and/or immunohistochemistry.

RESULTS

APP/PS1 mice showed severe declines in spatial learning and memory compared with their wild-type littermates, which were not attenuated by aerobic exercise combined with antioxidative treatment. The pathologic analysis revealed that Aβ deposition and production, oxidative stress, glial inflammation, and synaptic loss were not mitigated in the brain of exercised APP/PS1 mice, compared with the sedentary APP/PS1 animals.

CONCLUSION

This study reveals that a combined treatment of aerobic exercise plus antioxidative stress does not counteract pathophysiology in the moderate- or mid-stages of AD.

摘要

目的

本研究评估了有氧运动和抗氧化应激联合治疗对中度阿尔茨海默病(AD)的综合治疗效果。

方法

10 月龄的 APP/PS1 小鼠接受乙酰半胱氨酸抗氧化治疗,并进行 6 周的有氧运动。通过 Morris 水迷宫测试空间学习和记忆,并用 Thioflavin-S 染色定量检测前脑的 β-淀粉样蛋白(Aβ)斑块沉积。通过 Western blot 和/或免疫组织化学测定海马中的可溶性 Aβ1-42、β-分泌酶、γ-分泌酶、氧化和抗氧化应激标志物硝基酪氨酸和过氧化物酶 1、神经胶质标志物胶质纤维酸性蛋白和钙结合衔接分子 1、以及突触蛋白突触小体蛋白的水平。

结果

与野生型同窝仔相比,APP/PS1 小鼠的空间学习和记忆能力严重下降,而有氧运动结合抗氧化治疗并不能减轻这种下降。病理分析显示,与久坐不动的 APP/PS1 动物相比,运动的 APP/PS1 小鼠大脑中的 Aβ 沉积和产生、氧化应激、神经胶质炎症和突触丢失并没有得到缓解。

结论

本研究表明,有氧运动加抗氧化应激的联合治疗并不能对抗 AD 中晚期的病理生理变化。

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